The lipocalin beta-lactoglobulin (BLG) is a major protein compound in cow’s milk, and we detected it in cattle stable dust. BLG may be a novel player in the farm protective effect against atopic sensitization and hayfever. In previous studies, we demonstrated that only the ligand-filled holo-form of BLG prevented sensitization to itself. Here, we investigated whether holo-BLG could, in an innate manner, also protect against allergic sensitization to unrelated birch pollen allergens using a murine model. BALB/c mice were nasally pretreated four times in biweekly intervals with holo-BLG containing quercetin–iron complexes as ligands, with empty apo-BLG, or were sham-treated. Subsequently, mice were intraperitoneally sensitized two times with apo-BLG or with the unrelated birch pollen allergen apo-Bet v 1, adjuvanted with aluminum hydroxide. After subsequent systemic challenge with BLG or Bet v 1, body temperature drop was monitored by anaphylaxis imaging. Specific antibodies in serum and cytokines of BLG- and Bet v 1-stimulated splenocytes were analyzed by ELISA. Additionally, human peripheral blood mononuclear cells of pollen allergic subjects were stimulated with apo- versus holo-BLG before assessment by FACS. Prophylactic treatment with the holo-BLG resulted in protection against allergic sensitization and clinical reactivity also to Bet v 1 in an unspecific manner. Pretreatment with holo-BLG resulted in significantly lower BLG-as well as Bet v 1-specific antibodies and impaired antigen-presentation with significantly lower numbers of CD11c+MHCII+ cells expressing CD86. Pretreatment with holo-BLG also reduced the release of Th2-associated cytokines from Splenocytes in BLG-sensitized mice. Similarly, in vitro stimulation of PBMCs from birch pollen allergic subjects with holo-BLG resulted in a relative decrease of CD3+CD4+ and CD4+CRTh2 cells, but not of CD4+CD25+CD127− Treg cells, compared to apo-BLG stimulation. In conclusion, prophylactic treatment with holo-BLG protected against allergy in an antigen-specific and -unspecific manner by decreasing antigen presentation, specific antibody production and abrogating a Th2-response. Holo-BLG therefore promotes immune resilience against pollen allergens in an innate manner and may thereby contribute to the farm protective effect against atopic sensitization.
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Gender-specific differences are evident in food intolerance and allergy. In this review, we will highlight and summarize the dissimilarities in prevalence of adverse food reactions, focusing on IgE-mediated food allergies and intolerances regarding frequency of symptoms and predisposing factors. After puberty, females suffer more frequently from food-related symptoms than males. Several factors may be responsible for this observation, for example hormonal effects, gender-specific behavior, perception of risk, or intake of medications. In this context, concrete studies related to adverse food reactions are still lacking.
equally contributed.This is an open access article under the terms of the Creat ive Commo ns Attri butio n-NonCo mmerc ial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
To the Editor, Based on our previous molecular studies with ligands for lipocalin and lipocalin-like proteins, we predicted that the active vitamin D metabolite vitamin D3 (VD3) could bind into the intramolecular pocket of the major birch pollen allergen Bet v 1 (Bet v 1.0101), 1,2 transforming it from apo (empty) to holo-Bet v 1. As VD3 per se is able to modulate innate and adaptive immune responses, 3 we hypothesized that the binding of this immunomodulatory molecule would modify the allergenicity of Bet v 1.In a first step, we analysed VD3 binding to Bet v 1 by in silico docking analysis, in vitro ANS competition assay and IZ-VDRE cell reporter assay (Figure 1). In silico calculations based on the crystal structure of the Bet v 1-naringenin complex (PBD entry 4A87) (Figure 1A) rendered an affinity energy of −9.9 kcal/mol, corresponding to a dissociation constant of 0.055 µmol/L. The calculated affinity of VD3 to Bet v 1, being thus 6-times stronger than of vitamin A metabolite retinoic acid, 1 could be supported by in vitro assays. First, in an ANS competition assay, VD3 dose-dependently displaced ANS from Bet v 1 (Figure 1B). For the second assay, we used the human IZ-VDRE cell line stably transfected with vitamin D response elements VDRE-I from the human CYP24A1 promoter and expressing the gene for luciferase under the control of VDRE. 4 The This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
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